Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms

Abstract

Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.

HER2 Protein Overexpression and Gene Amplification in Tubo-Ovarian High-grade Serous Carcinomas

“…Woo et al (17) found HER2 gene amplification by FISH (defined as HER2/CEP17 ratio ≥ 2) in 1 of 31 serous carcinomas arising from fallopian tube/ovary; interestingly that case was scored as 0 on IHC. Mohammed et al (19) showed HER2 protein overexpression (3+ on IHC) in 1 of 53 ovarian serous carcinomas which did not show HER2 gene amplification (defined as ≥ 6 spots/cell) by chromogenic in situ hybridization. In a multi-center study on HER2 status in ovarian carcinomas, Tuefferd et al (7) used slightly different criteria for HER2 gene amplification FIG.…”

Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells

“…HER2 is a proto-oncogene which encodes a transmembrane glycoprotein, and its over-expression is involved in the regulation of abnormal proliferation, differentiation and anti-apoptotic processes [12][13]. The HER2 gene is over-expressed in many malignant tumors [14] and trastuzumab, which targets HER2, has been successfully used in the treatment of metastatic breast cancer with HER2-overexpression [15].There has been recent study on HER2 expression in ovarian cancer and its relationship with prognosis [16], and some researchers have found that HER2 gene expression has a key role in the occurrence and development of epithelial ovarian cancer; with the 5-year survival rate of patients with HER2 over-expression significantly decreased [17], suggesting it might be used as a poor prognostic factor.…”

Histopathological discrepancy and variation of surgical management in mucinous ovarian cystadenoma and pseudomyxoma peritonei

“…It seems that positive HER2 protein was not detected in normal or benign tumor. Borderline tumors show HER2 positive staining, but mostly no overexpression [16] . Chromogenic in situ hybridization (CISH) analysis was calculated from 20 tumor cell nucleus with ratio of HER2/CEP17 (cystadenoma) and HER2/Cen17 (pseudomyxoma).…”